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Tuesday, September 02, 2008

Question from Karl - Possibility that Henry VIII was the cause of the high mortality of his offspring

Henry VIII had little luck in establishing his dynasty. The number of miscarriages and stillbirths that his wives suffered seem excessive, even taking into account the time period when there was a high mortality. This is in sharp contrast to other contemporary royals, and even Henry's mother, Elizabeth of York. Would it be possible for the fault to lie with Henry himself? This would mean that Henry carried a balanced translocation, probably a new mutation. This could explain the miscarriages, stillbirths and possibly early death from cancer of Mary Tudor. If this were considered possible, would there be any way of extracting DNA to check this hypothesis.

9 comments:

PhD Historian
said...

Testing for translocation is very different from the type of DNA testing done to determine biological relationships of deceased or living persons, as I understand the two processes. Testing for translocation involves karyotyping, or the mapping of whole chromosomes. DNA testing of the kind used for genealogical testing looks deeper to the inside of the individual chromosomes at the DNA itself, especially DNA sub-units called alleles. Think of karyotyping as looking at various sizes and shapes of filing cabinets and genealogical DNA testing as opening the drawers of the filing cabinet to look at the contents of multiple individual files.

The problem is one of sampling. Genealogical testing requires only a small (even minute) sample and can usually be conducted using only the Y and/or X sex-linked chromosomes, without having a full complement of 23 pairs of chromosomes normally found in human cells. Karyotyping requires a sample of greater purity and the presence of all 23 intact pairs of chromosomes. While a DNA sample for genealogical testing might be easily obtained from the remains of both Henry VIII and Katherine of Aragon, I believe it is exceedingly unlikely that a sufficiently pure and complete sample could be obtained for karyotyping.

Even without the possibility of answers through testing (which is unlikely even to be attempted, given that opening Henry VIII's grave would require the current queen's consent), Karl proposes an interesting theory. Chromosomal translocation issues have been found to contribute greatly to the incidence of repeated miscarriages in modern women and to the early death of their children. If a translocation occurred as a new mutation in Henry VIII, rather than being inherited by him from either parental line, that would explain why neither of his sisters are reported to have suffered numerous miscarriages.

But the "fault" could as easily lie with Katherine of Aragon and not with Henry. One would need first to gather circumstantial evidence by examining the available pregnancy histories of Katherine's mother and sisters to determine whether any (or many) of them were similarly prone to multiple miscarriages and/or death of children in the first year after birth. If there is a history of such, the "fault" may not have been Henry's. One might also look at other abnormalities in Katherine's family tree, especially those now known to be genetically linked, for evidence of a wider pattern of genetic defects.

The only other female with whom Henry conceived pregnancies and for whom a reasonably detailed history of pregnancies is known is Anne Boleyn. (His mistresses must be excluded from the "study" on the grounds that Henry acknowledged only one bastard, Henry Fitzroy.) Anne had a total of perhaps 3 pregnancies, the last two of which ended in miscarriage, a high ratio but not conclusive evidence. Other women of the era reportedly suffered two miscarriages in rapid succession but later went on to deliver multiple healthy and surviving infants (e.g.: Frances Brandon Grey). Anne's miscarriages could have been induced by many things other than a genetic abnormality transmitted by Henry, including simple stress, or even the alcohol consumption mentioned by a previous questioner.

The theory is a facinating one, but I doubt that it can ever be reliably tested. And until it can, I am inclined to think that the "issue" was with Katherine, not Henry. Physical abnormalities in the mother (from infection to structural defect) are statistically a much greater cause of miscarriage than are chromosomal translocations contributed by the father.

Looks like you already got some detailed information on genetic mutations.

If you are looking to explore more reasons for Henry’s miscarriages then you could also consider the impact Henry’s diet had on his ability to conceive and produce viable pregnancies. Historian Susan Maclean Kybett has a really interesting (albeit unpopular) theory that many of Henry’s health problems were due to him having scurvy (not Syphilis). Henry’s diet of mostly meat could easily have led to deficiencies in Vitamin b12 too which has also shown to cause miscarriages in women. More info here:http://findarticles.com/p/articles/mi_m0ISW/is_2001_July/ai_76445709

I tend to feel that a women’s diet often gets blamed for miscarriages, but new research is showing that the man’s diet is equally as important. I saw a really interesting documentary where doctors fed one guy junk food and the other a healthy diet for weeks and then raced their sperm. The guy who was the junk food addict had slower and literally weaker sperm. I wish I could remember the name of the show because it was hilarious…but I can’t. It was on late night and I was little distracted by the concept of racing sperm.

Anyway, you could argue that nutritional deficiencies in a father and mother’s diet could lead to miscarriages.

bearded lady, I believe the scurvy theory is unpopular because it is not tenable. A diet of largely meat does not cause scurvy, lack of vitamin C does. And Henry's love of vegetables and especially of fruit is very well documented. He sent his gardeners to the continent to get fruits of all kind that could be grown in England and he did grow them and ate them. He was especially fond of oranges that Katherine of Aragon had introduced into England.

Also, as young man (during his marriage to Katherine and Anne Boleyn and on into his marriage with Jane Seymour) he was considered extremely healthy and vigorous. Virtually every ambassador to the English court noted that in dispatches to their home countries.

I think his health problems in later years is more indicative of Type II diabetes and possibly some other metabolic-related diseases than it is of scurvy.

I feel extremely sorry for Henry in a lot of ways. He seems to have become a lightning rod for for any theory anybody wants to propound, and in most cases, they don't even bother to check the actual evidence.

Karl, many of the latest medical information I've run across on Katherine of Aragon is of the opinion that she actually died of melanoma. If that is the case, and there is any genetic connection to her daughter's cancer, it would have come through her, not Henry. The Tudors, in fact, seem to have been fairly free of cancer.

I know everyone loves to theorize about famous people’s health problems (there’s a whole book written about the health of all our past presidents!) but I would not say that the scurvy theory is impossible.

Yes, Henry did love his marmalade and he certainly did have the occasional vegetable, but rarely in the winter months and scurvy is a very seasonal disease. And yes, records show that he got gifts of seasonal fruit from France but scurvy can actually develop slowly over a span of thirty years when fresh fruits and vegetables are not eaten on a regular basis. Henry did not eat them regularly and they were rarely fresh. Symptoms can also develop within 6 weeks- about the amount of time Henry fasted during Lent when he would be most deprived of nutritional foods.

Symptoms include:

-itching spots (Henry’s doctors thought he had smallpox) -loose teeth.-horrible breath-can retain healthy appetite but have erratic mood swings-ooze out nasty stuff from a wound. -build-up of fluid in the eyelids, forehead, cheeks, and temporal muscles

Henry had all these symptoms. Of course, you could argue that this sounds an awful like Diabetes too. Maybe he did have Diabetes. But diabetes was diagnosed well before Henry’s day (although doctors did not call it diabetes.) Doctors diagnosed it by tasting urine. yum! A sweet taste was a clear sign of the disease. I could be wrong, but I don’t remember reading anything about Henry’s urine being sweet. (I was tempted to post this as a question but I didn't want to risk Lara thinking I was an absolute freak)

Getting back to the original question, I still think Henry’s diet is worth exploring as a cause for miscarriages. We tend to have a myopic view of scurvy because it is so rare today, but it was very common in the 16th century.

"Anne's miscarriages could have been induced by many things other than a genetic abnormality transmitted by Henry, including simple stress"

Stress does not induce miscarriage.

I am the carrier of a balanced translocation and must admit that I have wondered at the seemingly worse than usual bad luck of Henry's brood. He had at least one child who died suddenly in infancy, multiple miscarriages, years of trying fruitlessly, and an apparent preterm birth; and all with multiple women. This does point to some type of genetic defect. However, the infants who were born and died were not recorded as having deformities or illnesses. If these babies/fetuses were not viable due to an unbalanced translocation, dysmorphic features, seizures, birth defects, and feeding problems would have been very likely.

I do think there was *something* genetic going on, but not this. Maybe a single-gene defect, or something that caused metabolic or cardiac disorders. Diet is extremely important, but many of the most populated places in the world are also the most poverty stricken and poorest.

I'm coming very late to the discussion; but Henry's sister Margaret had six children with James IV of Scotland and only the future James V survived. The younger sister Mary had four children with Charles Brandon one son died at about age six and the second at about age eleven. Does make you wonder about their genetics.

Infant mortality was high in that age, eveyweher in the world, so it's not a wonder that Henry's wives lost so many children.

In my opinion the reason was the high stress in which they lived. The main culprit is Henry, of course, who wasn't able to provide security and relibility to his wives. I am just watching at The Tudors, which includes many fictional ideas, but very well depicts the atnosphere of that age. Frankly speaking if I were a woman, I wouldn't wanted to give birth to any child of this monstruous king.

I think that it is possible that Henry VIII carried a Balanced Translocation. It is not always the case that a disability resulting from a partial trisomy or monosomy would not be obvious simply by looking at a newborn. If the breakpoints of the translocated Chromosome were relatively small it is possible that it would not have been obvious at all. It would also depend on the genetic material involved.

It could also account for the amount of stillborns, miscarriages and babies that died shortly after birth.

I would assume that Henry VIII's Balanced Translocation was indeed de novo as there is no evidence that anyone else in his family had the same problems reproductively as Henry did. It is possible that his children could have inherited it and could have accounted for Mary's fertility problems.

Of course there is no way to tell. Balanced Translocations are thought to occur in 1 in 500 people so it is certainly plausible.

I think it's highly likely that Henry VIII had a balanced translocation. His sisters were likely not carriers of the translocation, and thus were unaffected. (Although it's possible that Mary Tudor was a carrier, seeing as she had only 4 children in an 18 year marriage and only 2 survived to adulthood.)

Anyway, in BT carriers, there are 16 possible chromosomal combinations, 2/16 are balanced and therefore normal and viable. 1/16 carries the BT, and 1/6 is without the translocation and is normal. It is equally possible to be a carrier as to be normal, if you are balanced. The other 14/16 chromosomal combinations are unbalanced and therefore either do not make it to term, do not live long, or have severe defects.

In Henry VIII's case, I suspect that his translocation is a small or medium-sized break. This would account for the combination of children who lived for a short time and as well as the miscarriages. It would also account for the fact that there were so many known miscarriages. People with large breaks usually miscarry at 5 - 7 weeks or earlier, and many don't even know that they are pregnant. People with large breaks do not make it to term and the fact that several of these children did suggest that these were small-medium size breaks.

Additionally, I don't think that the BT was de novo in Henry VIII. If you look at the children that his parents had, you see a similar pattern of infant death and early childhood death. There were 8 children born, but only 3 made it to adulthood. Arthur being the question mark, as I'm not aware of developmental problems with him, although I also suspect that these would have been hidden if there were any. The question then becomes how far back did it go and where did it start? It seems to me that the translocation started somewhere in the Beaufort line, most likely with John Beaufort (1st Duke of Somerset). That's my 2 cents!